The research team, led by Roger Y. Tsien, Ph.D., professor of Chemistry and Biochemistry in UCSD’s Department of Pharmacology and Howard Hughes Medical Institute investigator, found that high levels of insulin can block the stress hormone catecholomine. For normal metabolism to occur, the body needs a balanced input of two types of hormones: insulin and catacholomines.

“Somehow, insulin knows how to specifically block catecholomine-induced PKA, but not other molecules,” said Christopher Hupfeld, assistant professor of Medicine in the UCSD Division of Endocrinology and Metabolism. “When the body has a constantly high level of insulin, this energy-release stimulus is lost.”

In order to understand the mechanisms of insulin resistance present in Type II diabetes, the researchers used a new breed of cellular enzyme reporter to track PKA. The reporter is a “marker” protein, created with a special fluorescent tag so that scientists can physically view the protein under a microscope and watch how the live cell works in real time.

The PKA is activated inside the adipocyte cell, the major site of energy storage in the body where many aspects of metabolism are controlled. There, energy is stored in the form of triglycerides, commonly known as fat. If a person is obese, excess triglycerides are stored in the adipocytes.

“If insulin levels get too high for too long a time – which happens in type II diabetes –the normal catecholamine signal that triggers energy release can be drowned out. This can lead to excessive energy storage in the adipocyte,” said Hupfeld. “This may be one reason why chronic obesity and Type II diabetes are often seen together.”

“By correcting this hormonal imbalance, we may at some point improve treatment options,” said Hupfeld.